title: Efficacy and safety of abiraterone acetate in an elderly patient subgroup (aged 75 and older) with metastatic castration-resistant prostate cancer after docetaxel-based chemotherapy.
abstract: BACKGROUND
  Metastatic castration-resistant prostate cancer (mCRPC) is a disease that primarily affects older men. Abiraterone acetate (AA), a selective androgen biosynthesis inhibitor, in combination with low-dose prednisone (P) improved overall survival (OS) in a randomised trial in mCRPC progressing after docetaxel versus placebo (PL) plus P.
  
  
  OBJECTIVE
  To examine the efficacy and safety of AA plus P versus PL plus P in subgroups of elderly (aged ≥ 75 yr) (n=331) and younger patients (<75 yr) (n=863).
  
  
  METHODS
  We conducted a post hoc analysis of a randomised double-blind PL-controlled study in mCRPC patients progressing after docetaxel chemotherapy.
  
  
  METHODS
  Patients were randomised 2:1 to AA (1000 mg) plus low-dose P (5mg twice daily) (n=797) or PL plus P (n=398).
  
  
  METHODS
  Primary end point was OS. Secondary end points were time to prostate-specific antigen (PSA) progression (TTPP), radiographic progression-free survival (rPFS), and PSA response rate. Treatment differences were compared using the stratified log-rank test. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). The key limitation was the post hoc analysis.
  
  
  CONCLUSIONS
  Elderly patients treated with AA plus P showed improved OS (HR: 0.64; 95% CI, 0.478-0.853; p=0.0022), TTPP (HR: 0.76; 95% CI, 0.503-1.155; p=0.1995), and rPFS (HR: 0.66; 95% CI, 0.506-0.859; p=0.0019), and higher PSA response rate with relative risk (HR: 4.15; 95% CI, 2.2-8.0]; p ≤ 0.0001) compared with patients treated with PL plus P. Grade 3/4 adverse events occurred in 62% of elderly patients and in 60% of patients aged <75 yr treated with AA plus P. Incidences of hypertension and hypokalaemia, although increased in the AA plus P arm, were similar in both age subgroups and readily managed.
  
  
  CONCLUSIONS
  AA improves OS and is well tolerated in both elderly patients and younger patients with mCRPC following docetaxel, hence providing an important treatment option for elderly patients who may not tolerate alternative therapies with greater toxicity.
  
  
  BACKGROUND
  ClinicalTrials.gov, identifier NCT00638690.
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Electronic address: p.mulders@uro.umcn.nl.
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Molina
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Marberger
authors.affiliation: University of Montreal, Montreal, QC, Canada.
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.affiliation: British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: Thian
authors.initials: T
authors.lastname: Kheoh
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Haqq
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D000069501:Abiraterone Acetate; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007008:Hypokalemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D043823:Taxoids; D000077143:Docetaxel; D013254:Steroid 17-alpha-Hydroxylase; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate; D011241:Prednisone
keywords: Abiraterone acetate; Elderly; Metastatic castration-resistant prostate cancer